Potassium (K) plays an important role in several cellular homeostasis. K deficiency causes derangements of various tissue and organ functions. In order to study the effect of chronic K deficiency and subsequent to K repletion on extrarenal potassium homeostasis, adult male and female Sprague-Dawley rats were divided into 2 groups. K depletion was induced by feeding with a K-deficient diet and deionized water ad libitum for 120 days. The other group was paired-fed with normal rat chow at the same amount consumed by the former group serving as controls. During K depletion, rats had low food intake and their growths were retarded compared to control period. Polyuria, polydipsia, and a reduction in urinary K+ excretion were observed. Dietary K deprivation for 16-17 weeks resulted in a significant decreased in plasma K+ concentration to 1.5-2 mEq/L whereas plasma Na+ concentration was virtually not changed. In addition, K deficiency caused a metabolic alkalosis, a reduction in K+ but an accumulation in Na+ contents in soleus and extensor digitorum longus muscle. However, 2 weeks repletion of K by feeding normal rat chow resulted in marked increases in body weight, rapid restoration in water intake and urine output. Moreover, changes in plasma and muscles electrolyte and acid-base status were also reversible. To investigate extrarenal potassium homeostasis; K-depleted (n=7), K-supplemented (n=8), diet-restricted (n=11), and normal-untreated rats (n=11), were anesthetized with Inactin i.p.. Functional nephrectomy and adrenalectomy were performed and acute K-loading was challenged by intravenous infusion with KCl at a dose of 2 mEq/kg/hr for 1 hour. This resulted in elevations of plasma K+ concentration and muscle K+ content in all groups. The increment in plasma K+ concentration was significantly lower in K-depleted rats vs. normal rats (1.9±0.3 vs. 3.9±0.1 mEq/L, p<0.001), whereas the increases in muscle K+ content was higher than those in other groups. Values are means±S.E.M., compared by ANOVA. Furthermore, following KCl infusion blood pH was significantly decreased (p<0.05) and plasma Na+ concentration was increased (p<0.05) in K-depleted rat but those in the other groups were virtually not changed. These results were related to a greater K uptake in K-depleted rat indicating an alteration in extrarenal potassium disposal after chronic K deficiency. It is concluded that following KCl infusion the K+ ion may be an appropriate stimulus that leads to a marked activation of the residual Na+-K+ pump in K-depleted rats sufficient to lower plasma K+ concentration than in normal rats. This effect may be mediated by insulin as well as an accumulation of Na+ in muscle, increase in extracellular HCO3- and metabolic alkalosis developed after chronic K deficiency. However, alteration in extrarenal potassium disposal is completed reversed after K repletion.